1. Field of the Invention
The present invention relates to a combination of dosage units for alleviating/treating respiratory ailments such as nasal congestion and to a method of alleviating/treating respiratory ailments which uses this combination of the dosage units. The dosage units comprise one or more first dosage units comprising a first sympathomimetic agent, i.e., pseudoephedrine and/or a pharmaceutically acceptable salt thereof, and one or more second dosage units comprising a second sympathomimetic agent, i.e., phenylephrine and/or a pharmaceutically acceptable salt thereof.
2. Discussion of Background Information
Pseudoephedrine and its pharmaceutically acceptable salts are powerful sympathomimetic agents used for the control of allergic manifestations and for decongestion of respiratory airways in human subjects. However, pseudoephedrine containing products often give rise to excessive plasma concentrations when ingested according to dosage directions. These levels can reach blood concentrations that are 75% to 200% higher than the concentration needed for therapeutic effects.
Current dosage schedules of pseudoephedrine containing products available in the United States contain labels that instruct adult patients to ingest a maximum dosage of 60 mg of immediate release pseudoephedrine hydrochloride or other pharmaceutically acceptable salts thereof every 4 to 6 hours, but not to exceed 240 mg in a 24 hour period. Sustained release oral dosage forms of pseudoephedrine instruct an adult person to ingest 120 mg per dose every 12 hours, or 240 mg per dose in case of a 24 hour dosage form.
Regardless of whether the ingested dosage form is an immediate or a controlled release dosage form, at the end of the dosage cycle the plasma concentration of pseudoephedrine will still be above or barely below the therapeutic level, since the half life of pseudoephedrine is about 6 to 8 hours. Accordingly, it is inevitable that the second and all subsequent doses will exceed the minimum therapeutic plasma concentration by 75% to 200%, depending on whether the dosage is taken every 4 hours or every 6 hours or is taken in the form of a controlled release dosage unit.
There is no question that excessive therapeutic levels of pseudoephedrine of the order of 75% to 200% will more likely provoke the known side effects thereof such as, e.g., cardiovascular stimulation with elevated blood pressure, tachycardia or arrhythmias, central nervous system stimulation with resulting nervousness, excitability, restlessness, dizziness, weakness, insomnia, anxiety, tremors, hallucinations, skin rashes, urinary retention, headache and drowsiness. Large doses of pseudoephedrine may also cause lightheadedness, nausea and/or vomiting. Pseudoephedrine may further increase the irritability of the heart muscle and may alter the rhythmic function of the ventricles, especially in large doses or when administered to patients who are hypersensitive to the myocardial effects of sympathomimetic drugs.
A way to prevent excessive plasma concentrations of pseudoephedrine would be to allow the blood levels of pseudoephedrine to fall low enough so that the second and subsequent dosages do not add excessive amounts of the agent into the blood stream. However, this solution appears contrary to both precedent and conventional medical practice, since it would leave the patient suffering from respiratory ailments relating to allergies, common colds, or other common types of respiratory ailments for which sympathomimetics are indicated without adequate medication for several hours each day.
In view of the foregoing, there is a need to avoid excessive plasma concentrations of pseudoephedrine during the continued administration of pseudoephedrine dosage forms without interrupting the therapeutic effect provided by pseudoephedrine.